IF 3.5 2区 医学 Q2 GENETICS & HEREDITY
Yehezkel Ben-Ari, Étienne É Danchin
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引用次数: 0

摘要

大脑发育涉及脆弱生物过程的顺序表达,包括细胞增殖、细胞程序性死亡、神经元迁移、突触和功能单元的形成。所有这些过程都涉及依赖基因和活动的事件,这些事件可能会被许多外在和内在环境因素所扭曲,包括压力、微生物群、炎症信号、荷尔蒙信号和表观遗传因素,从而导致在子宫内出生的失调,这些失调后来表现为自闭症谱系障碍(ASD)和其他神经发育障碍。预测和治疗这类疾病需要一个包括发育生物学各个方面的概念框架。在此,我们以 ASD 的高发病率为例,首先讨论遗传方法的内在局限性,特别是广泛使用的双胞胎研究和 SNPs。然后,我们回顾了一长串可能偏离发育序列的子宫内事件,这些事件导致未成熟的错位和错联神经元组合产生持续的异常活动,而这正是 ASD 的直接原因。从临床角度看,我们建议分析非遗传的孕产数据,以便及早预测多年后会患上 ASD 的婴儿,从而促进早期心理教育技术的发展。随后,能够选择性沉默畸形未成熟网络的药物将为治疗提供广阔前景。总之,了解发育过程对于预测、理解和治疗 ASD 以及其他大多数在子宫内出现的疾病至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Limitations of genomics to predict and treat autism: a disorder born in the womb.

Brain development involves the sequential expression of vulnerable biological processes including cell proliferation, programmed cell death, neuronal migration, synapse and functional unit formation. All these processes involve gene and activity-dependent events that can be distorted by many extrinsic and intrinsic environmental factors, including stress, microbiota, inflammatory signals, hormonal signals and epigenetic factors, hence leading to disorders born in the womb that are manifested later in autism spectrum disorders (ASDs) and other neurodevelopmental disorders. Predicting and treating such disorders call for a conceptual framework that includes all aspects of developmental biology. Here, taking the high incidence of ASDs as an example, we first discuss the intrinsic limitations of the genetic approach, notably the widely used twin studies and SNPs. We then review the long list of in utero events that can deviate developmental sequences, leading to persistent aberrant activity generated by immature misplaced and misconnected neuronal ensembles that are the direct cause of ASD. In a clinical perspective, we suggest analysing non-genetic maternity data to enable an early prediction of babies who will develop ASD years later, thereby facilitating early psycho-educative techniques. Subsequently, agents capable of selectively silencing malformed immature networks offer promising therapeutic perspectives. In summary, understanding developmental processes is critical to predicting, understanding and treating ASD, as well as most other disorders that arise in the womb.

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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
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